Biology Reference
In-Depth Information
biochemical reactions (
Baker, Sept, Joseph, Holst, & McCammon, 2001
). The rela-
tionship between the electric field and the charge in a system is described by Max-
well's equations (
Callenberg et al., 2010
). One of the most representative models for
the evaluation of electrostatic properties is the Poisson-Boltzmann equation. This is
a second-order nonlinear elliptic partial differential equation that links the electro-
static potential to the dielectric properties of the solute and solvent, the ionic strength
of the solution and the accessibility of ions to the solute interior, and the distribution
of solute atomic partial charges (
Baker et al., 2001
).
Similarly as for NMA, there are not many examples of applications of electro-
statics studies for GPCRs and their dimerization. As little is known about the mech-
anism and stability of the class A GPCR dimerization, we used APBS for modeling
biomolecular solvation through resolution of the Poisson-Boltzmann equation for
describing electrostatic interactions between molecular solutes in a given medium
to study the various dimerization properties of these receptors (
Kaczor, Lopez,
Pastor, & Selent, 2010
). Recent studies suggest that stable complexes are formed
by the
b
1
-adrenergic, the dopaminergic D
2
, and
the muscarinic M
1
receptor form rather transient complexes. Going into details,
the low dielectric membrane-like model was incorporated with the APBS membrane
tool in order to crudely represent the nonpolar membrane environment; dielectric
constants of 80, 10, and 2 for water, protein, and membrane interiors were intro-
duced, respectively. Thereby, computation of the electrostatic potential for different
GPCRs suggests that the stability of the receptor dimer corresponds to the distribu-
tion pattern of the electrostatic potential. The computed electrostatic potential for
various monomers of class AGPCRs suggests that receptors, forming transient dimer
complexes (
b
2
-adrenergic receptor, while the
b
1
,D
2
, and M
1
receptor), exhibit a surface dominated by a positive
(blue) electrostatic potential, while the surface of the
b
2
-adrenergic receptor, forming
a stable dimer complex, exhibits a more balanced set of positive and negative
electrostatic patches.
5.4.2
Software
One of the most popular software for electrostatics calculations is APBS, which is
used for modeling biomolecular solvation through solution of the Poisson-Boltz-
mann equation (
Baker et al., 2001
). Another freely available program is called
APBSmem, and it is designed for carrying out the electrostatics calculations in
the presence of a membrane (
Callenberg et al., 2010
).
Acknowledgments
This chapter was partially prepared during the postdoctoral fellowship of Agnieszka A. Kac-
zor, under Marie Curie IEF fellowship. Jana Selent acknowledges support from the Instituto de
Salud Carlos III FEDER (CP12/03139) and the La MARAT
ยด
de TV3 Foundation, Grant num-
ber 091010. Part of the calculations was performed under a computational grant by
